Vitamin D

Cancer Prevention and Other New Uses

By Russell Martin

The past year has produced stunning research findings concerning vitamin D’s potential role in preventing and perhaps even treating cancer.

Scientists are examining the use of vitamin D to reduce the risk of no fewer than 17 different types of cancer, ranging from colon, breast, and prostate cancers to ovarian, esophageal, renal, and bladder cancers. Moreover, researchers believe vitamin D may even improve treatment outcomes in people already diagnosed with cancer. A recent review article estimated that 50,000-70,000 Americans die prematurely from cancer each year due to insufficient intake of vitamin D.1

Emerging research suggests that vitamin D also has applications in promoting bone strength, as well as in mitigating autoimmune conditions such as multiple sclerosis, type I diabetes, and rheumatoid arthritis. Other potential benefits include promoting dental and skin health, and helping to prevent stroke, metabolic syndrome, and musculoskeletal pain.

New research indicates that vitamin D acts through several mechanisms to help fight cancer. Studies suggest that the active form of vitamin D may help to promote cell differentiation and support apoptosis (programmed cell death), as well as help to prevent metastases and angiogenesis.2 Vitamin D’s role in supporting calcium absorption may also contribute to its ability to fight cancer, since calcium has been shown to decrease proliferation and induce differentiation in epithelial cells.1

Combating Colorectal Cancer

Vitamin D’s effects in reducing cancer risk have been studied most extensively in colorectal cancer, the second leading cause of cancer death in the US.3 A study in 2005 investigated the relationship between vitamin D intake, serum vitamin D levels, and colorectal cancer risk. Individuals with vitamin D intake of 1000 IU or more daily or with serum vitamin D (25-hydroxyvitamin D) levels of 33 nanograms per milliliter (ng/mL) experienced a 50% lower risk of colorectal cancer. A daily dose of 1000 IU of vitamin D is half the safe upper limit established by the National Academy of Sciences. According to the study authors, prompt public health action is needed to increase daily intake of vitamin D to 1000 IU and to raise serum levels of 25-hydroxyvitamin D. For some individuals, modest sunlight exposure may help achieve these optimal levels.4

An epidemiological review conducted in 2005 at Harvard Medical School corroborated vitamin D’s protective effects against colorectal cancer and noted that typical dietary intake of 200-400 IU per day is probably too low to confer appreciable benefits. The Harvard study noted that a person’s vitamin D status at the time of cancer diagnosis and treatment may influence survival.5

In the recent Polyp Prevention Trial, investigators analyzed several dietary factors in relation to the recurrence of adenomatous polyps in the colon.6 Adenomatous polyps are considered pre-malignant and may therefore be a harbinger of colon cancer. Low intake of calcium and vitamin D was associated with increased risk of recurrence of the pre-malignant polyps. Optimal vitamin D and calcium status may thus be an important preventive strategy against colon cancer.

Protecting the Prostate

Recent clinical trials suggest that vitamin D and its analogs promise to be important therapies for prostate cancer.7 Experimental evidence indicates that the active form of vitamin D promotes differentiation and inhibits proliferation, invasiveness, and metastasis of human prostate cancer cells.8,9

In a study conducted last year, investigators examined the relationship between sun exposure and prostate cancer. Comparing 450 men with advanced prostate cancer with 450 unaffected men, they found that those with a high level of sun exposure had a 50% lower prostate cancer risk than men with low sun exposure. The researchers believe sunlight helped protect the men against prostate cancer by promoting vitamin D synthesis. Because of the association between sun exposure and certain skin cancers, however, the scientists noted, “increasing vitamin D intake from diet and supplements may be the safest solution to achieve adequate levels of vitamin D.”9

The prostate is below the bladder and should be clear, but due to the presence of a tumor it appears cloudy. The urethra shows narrowing caused by the pressure from the tumor.

Another study in 2005 demonstrated a therapeutic role for vitamin D in prostate cancer. Sixteen men who had previously been treated for prostate cancer supplemented with 2000 IU daily of vitamin D. The investigators then monitored prostate-specific antigen (PSA) levels for over two years. PSA is a marker of prostate cancer recurrence or progression. In nine patients, PSA levels decreased or remained unchanged after vitamin D supplementation began. In patients with rising PSA levels, supplementation with vitamin D3 significantly lengthened the PSA doubling time, by an average of 75%. (The rate at which PSA increases or doubles is correlated with disease prognosis, with longer PSA doubling times associated with better outcomes.) These findings indicate that vitamin D may help to slow or prevent disease recurrence or progression in patients who have been treated for prostate cancer.10

Vitamin D has also been reported to benefit patients whose prostate cancer has metastasized to the bones. This patient population commonly develops vitamin D deficiency. Supplementing these individuals with vitamin D was found to reduce pain, boost muscle strength, and improve overall quality of life.11

Benefits for Breast Health

Several lines of evidence suggest vitamin D may help reduce the incidence of breast cancer. A prospective study published in 2005 examined the relationship of plasma vitamin D metabolites to breast cancer risk in a cohort of women enrolled in the Nurses’ Health Study. Blood samples were collected from study participants from 1989 to 1990 and analyzed for the vitamin D metabolites 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D. The study participants were followed until 1996. The researchers then compared blood samples from women who developed breast cancer with samples from cancer-free control subjects. High levels of both vitamin D metabolites were associated with a non-significantly lower risk of breast cancer. For both metabolites, the association was stronger in women aged 60 and older.12

In another line of study last year, investigators looked at the relationship between dietary vitamin D and calcium intake and breast density as measured by mammography.13

Mammographic density is considered a strong risk factor for breast cancer.14 Dietary intake of vitamin D and calcium was assessed in a group of women, aged 40-60, who had screening mammograms. Women who had a combined daily intake of 100 IU or more of vitamin D combined with 750 mg or more of calcium demonstrated decreased breast density compared to women with lower intakes of the two nutrients. This suggests that adequate consumption of vitamin D and calcium may reduce breast cancer risk by influencing breast tissue architecture.13

Improving Lung Cancer Survival

Vitamin D may help people with lung cancer to live longer, according to a study released in 2005. The most common cause of cancer death in American men and women, lung cancer can be challenging to treat effectively. The report found that men with early-stage non-small cell lung cancer who had higher vitamin D indices (based on dietary intake and exposure to sunlight) had improved recurrence-free survival rates compared to men with lower vitamin D intake and sun exposure.15 Another study conducted in 2005 demonstrated that the active form of vitamin D inhibited lung cancer metastasis in an animal model of the disease.16 These findings suggest that implementing vitamin D therapy may be critical to improving survival rates for lung cancer patients.

Additional scientific evidence suggests that optimal vitamin D status may be associated with reduced risk of many other forms of cancer. These include cancers of the bladder, esophagus, stomach, ovary, uterus, cervix, pancreas, larynx, oral cavity, and gall bladder, as well as Hodgkin’s and non-Hodgkin’s lymphomas.1

In addition to its effects against numerous cancers, vitamin D holds promise in preventing and alleviating autoimmune conditions and in optimizing the health of the gums, bones, and muscles.

THE SUNSHINE DEBATE

Because vitamin D is fat soluble, it can be stored in the adipose tissue of the body, presumably for long-term access. Much debate on vitamin D has focused on the need for dietary supplementation versus the body’s endogenous (internal) manufacture of the vitamin from sunlight exposure.

For those living in climates with greatly reduced angles of sunlight (the northern and southern parts of the globe) or where sunlight itself is rare, the need for supplementation is unchallenged. The human body is designed to obtain vitamin D from exposure to sunlight, with only brief exposure providing roughly 80-90% of the body’s vitamin D stores.17 Exposure of the entire body to sunlight may produce approximately 10,000 IU of vitamin D a day.18 To prevent the accumulation of toxic levels of vitamin D, the body naturally limits the amount of vitamin D it synthesizes from sunlight.19

For years, health advocates have suggested that sun exposure may contribute to cancer risk and sunscreen should be used for all sun exposure greater than 15 minutes. New evidence suggests, however, that vitamin D can in fact protect against several forms of cancer. While sunscreen may help protect against the deadliest skin cancer—melanoma—its effect of limiting vitamin D production could lead to a greater incidence of other cancers.20 That does not mean that sunscreens should not be used, as they can significantly protect against premature skin aging (and skin cancers). What this does tell us, however, is that in one way or another, it is critical that we obtain optimal levels of vitamin D.

Cancer occurs more frequently in dark-skinned people, the obese, and regions with limited exposure to ultraviolet B radiation from sunlight. Each of these factors is associated with low blood levels of vitamin D. Furthermore, cancer survival rates are lower when the diagnosis occurs in months of lower sunlight levels, suggesting a protective role of vitamin D. Studies suggest that vitamin D protects against numerous forms of cancer, including widely prevalent cancers such as those affecting the colon, prostate, breast, and lung.1,20

Preventing Multiple Sclerosis

Multiple sclerosis is an immune-mediated inflammatory and neurodegenerative condition of the central nervous system. Its symptoms include weakness, visual problems, and impaired coordination. Although its causes remain unknown, scientists suspect that multiple sclerosis may represent an autoimmune condition.

Investigators have established a strong link between multiple sclerosis incidence and geographic location, noting that areas with abundant sun exposure or plentiful dietary fish intake experience reduced risk. Multiple sclerosis occurs more often in people who lived in northern areas of Europe and North America during childhood, and less often in people who live closer to the equator.23 Individuals appear to retain the level of risk associated with the area in which they lived until age 15, even if they moved to a different area later in life.23 In Switzerland, multiple sclerosis rates are higher at low altitudes and lower at high altitudes, where UV light is more intense. In Norway, multiple sclerosis rates are higher inland, but much lower near the coast, where vitamin D3-rich fish is consumed regularly.24 Vitamin D, obtained through both sun exposure and diet, may be the factor responsible for the link between geography and multiple sclerosis risk.

Evidence suggests that vitamin D supplementation may decrease the lifetime risk of multiple sclerosis in women. Experimental data suggest the white matter of the brain that multiple sclerosis affects contains vitamin D receptors, and inadequate vitamin D during early development may predispose these cells to an early demise.25

Researchers have noted that administering the active form of vitamin D—1,25-dihydroxyvitamin D—to animals can completely protect them against an experimentally induced form of multiple sclerosis.24 According to the investigators, the active form of vitamin D may act as a selective immune system regulator that works to inhibit autoimmune disease.

Later research indicated that 1,25-dihydroxyvitamin D also helped to reduce multiple sclerosis disease activity in mice with an experimentally induced model of the disease.26 Based on this animal data, Dutch researchers postulated that multiple sclerosis patients may similarly benefit from optimal serum concentrations of vitamin D. Optimal vitamin D levels might not only help achieve immune-mediated suppression of disease activity, but also help decrease complications related to multiple sclerosis, such as muscle weakness, osteoporosis, and bone fractures.26

VITAMIN D BASICS

Technically, vitamin D is not a true vitamin. Since sun exposure can stimulate its synthesis in the body, it is not necessarily required in the diet, except in certain circumstances. Furthermore, its structure and mechanism of action more closely resemble those of a hormone than those of a vitamin.

Vitamin D occurs in nature in two main forms: vitamin D2, or ergocalciferol, and vitamin D3, or cholecalciferol. While vitamin D2 is obtained from plant sources, vitamin D3 can either be obtained through animal sources or synthesized in the skin when its precursor molecule absorbs light energy from ultraviolet B rays. Vitamin D can refer to either D2 or D3. In the liver, both are converted into 25-hydroxyvitamin D, the primary circulating form of vitamin D. Conversion into its active form, 1,25-dihydroxyvitamin D, occurs in the kidney. Pharmaceutical drug forms of vitamin D include calcitriol, doxercalciferol, and calcipotriene.21

Vitamin D’s most crucial role is regulating calcium and phosphorus concentrations in the serum. Vitamin D assists with absorption of these two minerals in the small intestine. When dietary intake of calcium is below optimal levels, vitamin D3 along with parathyroid hormone will move calcium from storage in the bone into the serum, where the body as a whole can use it.22

Because Vitamin D is found naturally in relatively few foods, supplementation in certain products, particularly milk, has become a main avenue for obtaining the vitamin. Foods that contain vitamin D include fatty fish such as tuna, sardines, herring, and mackerel, as well as eggs from hens that have been supplemented with vitamin D.21

Effects on Type I Diabetes

Some scientists believe that type I diabetes may be an autoimmune condition in which insulin-producing pancreatic beta cells are destroyed. Evidence from animal experiments and human observational studies suggests that vitamin D may help prevent type I diabetes, perhaps by acting as an immune system modulator.27

Researchers demonstrated that the pancreatic beta cells of mice contain receptors for 1,25-dihydroxyvitamin D. When they administered this active form of vitamin D to mice early in life, the animals demonstrated a reduced incidence of type I diabetes. However, when 1,25-dihydroxyvitamin D was administered later in the life span of mice, diabetes incidence was not affected. Vitamin D appears to limit the expression of certain cytokines, which may prevent the autoimmune attack on pancreatic cells that can lead to diabetes.28

Human studies likewise suggest that vitamin D may have a protective effect against type I diabetes. In a large-scale investigation, more than 12,000 pregnant women in Finland enrolled in a trial studying the relationship between vitamin D intake and type I diabetes in infants. After one year, children who supplemented with the suggested study dose of vitamin D (2000 IU per day) had a much lower risk of type I diabetes than children who did not supplement.29

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